Effect of Chronic and Short‐Term Erythropoietin Treatment on Random Flap Survival in Rats: An Experimental Study

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Abstract
The use of perioperative erythropoietin (EPO) therapy is gaining popularity to avoid blood transfusion and correct anemia in head and neck cancer surgery. The purpose of the study was to determine the effect of various doses and durations of EPO treatment on random flap survival. A McFarlane type random and musculocutaneous (3 x 10 cm) flap were elevated on the dorsum of each rat. Eighty-four male Albino rats were randomly assigned into seven groups (2 animals in each group): group I, control animals receiving placebo; group II, chronic EPO injections (50 U/kg); group III, chronic EPO injections (100 mg/kg); group IV, chronic EPO injections (150 mg/kg); group V, short-term EPO injections (50 mg/kg); group VI, short-term EPO injections (100 mg/kg); and group VII, short-term EPO injections (150 mg/kg). Rats in groups II to IV began to receive EPO 3 weeks (thrice weekly) before the construction of flaps, and rats in groups V to VII received EPO after flap elevation for 1 week (thrice) subcutaneously. Following 7 days of recovery, the area of flap survival was measured. Hematocrit and systolic blood pressure were followed weekly in all groups. Erythropoietin increased the hematocrit levels and systolic blood pressure in all groups, but significant increases were noted only in the long-term treatment groups. There was a significant increase in distal necrosis of random skin flaps after long-term EPO treatment (P <.05). However, short-term low and therapeutic doses of EPO improved flap survival significantly (P <.05). Long-term EPO treatment might have impaired flap survival because of direct or prostaglandin-mediated vasoconstriction, endothelin-induced hypertension, increased peripheral vascular resistance, hyperviscosity, and increased thrombosis. However, EPO might have enhanced flap survival because of its antioxidant effect and modulation of nitric oxide levels. Effects of EPO are controversial, and further research is necessary to delineate the dose and duration relationship and the exact mechanism of action on flap viability.